PROJECT SUMMARY Significance: Portal vein embolization (PVE) is a procedure that is performed to induce hypertrophy of the non- diseased future liver remnant (FLR) to a sufficient volume to enable surgical resection of the diseased portion of the liver. One of the most important factors governing FLR hypertrophy is the embolic agent used. A review of the literature indicates that embolization with cyanoacrylate glue (?glue?) induces the greatest amount of FLR hypertrophy. Despite this evidence, physicians in the United States prefer PVE using microspheres, which are technically easier to administer than glue; additionally glue is only FDA-approved for neurovascular indications. Development of an embolic agent FDA indicated for PVE that induces the same (or better) amount of FLR hypertrophy as glue but without the associated risks and challenges would represent a significant advance in standardizing PVE and have potential applicability in other embolization applications. Approach: In this Phase I SBIR, Arsenal Medical, will evaluate its shear-thinning biomaterial technology as a distal penetrating embolic (DPE) therapy for PVE. In order to be effective, complete and distal embolization of the portal vein and its branches is desired in order to minimize the formation of porto-portal collaterals, which diverts portal flow away from the FLR and reduces hypertrophy. Therefore, in Aim 1, we will use a PVE swine model to identify a formulation with shear-thinning properties that adequately responds to the dynamic blood flow environment such that maximal distal penetration and occlusion are achieved. Subsequently, in Aim 2, we will evaluate the kinetics of FLR hypertrophy (and determine any differences with distal penetration and/or porto-portal collateralization) following embolization with our material compared to glue. Success will be demonstration of FLR hypertrophy similar to or better than the glue. The proposed studies would be the first to characterize the impact of distal penetration of different embolic agents on porto-portal collateralization and subsequent FLR hypertrophy kinetics, filling an important void in the literature. Innovation: Our DPE biomaterial has unique shear-thinning properties, making it adaptive and responsive to blood flow, becoming a low viscosity fluid under high shear that penetrates and fills the portal vein and distal branches. As flow decreases due to the embolization procedure, the shear decreases, and the viscosity of the material increases. In doing so, an entire cast of the vasculature is generated that provides complete occlusion, eliminates re- canalization, and minimizes collateralization. Unlike glue, the solidification mechanism of the DPE is independent of its microenvironment, thereby allowing a longer working time and making distal penetration unsusceptible to injection rate. Further, the material is not adhesive, so there is no risk of adhesion to the catheter, and is formulated to be radiopaque, enabling visualization under fluoroscopy. Leading interventionalists have attested to the procedural simplicity of using the DPE with respect to preparation, delivery, and control during embolization.